Study of the effect of α-Synuclein on SNARE-mediated membrane fusion

dc.contributor.advisor Yeon-kyun Shin Feng, Wei
dc.contributor.department Biochemistry, Biophysics and Molecular Biology 2018-08-11T07:37:38.000 2020-06-30T02:27:50Z 2020-06-30T02:27:50Z Sat Jan 01 00:00:00 UTC 2011 2013-06-05 2011-01-01
dc.description.abstract <p>Neurotransmitter release is a precisely orchestrated process in terms of time and space in neuron. SNAREs have been identified to function as the basic machinery mediating membrane fusion during neutotransmitter release. Many forms of neurodegeneration initiate presynaptically, but few of their molecular mechanisms have been revealed clearly. α-Synuclein (α-Syn) is a highly conserved synaptic vesicle-associated protein. Aggregation of α-Syn is a major component of the Lewy bodies, which is characteristic of Parkinson's disease (PD). We studied the effect of α-Syn on SNARE-mediated membrane fusion using fluorescent methods. Bulk lipid mixing assay shows that α-Syn has a role of inhibition in fusion and this effect requires phosphatidylserine (PS) on the vesicles. Disease related α-Syn mutants, A30P and E46K, shows higher inhibition effect on the lipid mixing than wild type. Synaptotagmin-1 (Syt-1) is a Ca2+ sensor localized to synaptic vesicles and regulates neuronal exocytosis. C2AB, a soluble model of Syt-1 that lacks the transmembrane region, is shown here to accelerate the FRET significantly. This acceleration effect of lipid mixing also needs PS on the vesicles. α-Syn can inhibit C2AB's stimulatory effect to a large extent. Thus, α-Syn can inhibit SNARE-mediated membrane fusion event.</p>
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dc.identifier archive/
dc.identifier.articleid 1389
dc.identifier.contextkey 2798760
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath etd/10349
dc.language.iso en
dc.source.bitstream archive/|||Fri Jan 14 18:19:09 UTC 2022
dc.source.bitstream archive/|||Fri Jan 14 18:19:10 UTC 2022
dc.subject.disciplines Biochemistry, Biophysics, and Structural Biology
dc.subject.keywords alpha-synuclein
dc.subject.keywords membrane fusion
dc.subject.keywords Parkinson's Disease
dc.subject.keywords SNARE
dc.supplemental.bitstream thesisfigures.pdf
dc.title Study of the effect of α-Synuclein on SNARE-mediated membrane fusion
dc.type article
dc.type.genre thesis
dspace.entity.type Publication
relation.isOrgUnitOfPublication faf0a6cb-16ca-421c-8f48-9fbbd7bc3747 thesis Master of Science
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